title: An indirect role for NK cells in a CD4(+) T-cell-dependent mouse model of type I diabetes.
abstract: CD8(+) T cells kill pancreatic β-cells in a cell-cell contact-dependent mechanism in the non-obese diabetic mouse. CD4(+) T lymphocytes are also able to kill pancreatic β-cells, but they do not directly contact β-cells and may use another cell type as the actual cytotoxic cell. Natural killer (NK) cells could have this role but it is uncertain whether they are cytotoxic towards β-cells. Therefore, the requirement for NK cells in β-cell destruction in the CD4-dependent T-cell antigen receptor transgenic NOD4.1 mice was examined. NK cells failed to kill β-cells in vitro, even in the absence of major histocompatibility complex class I. We observed only 9.7±1.1% of islet infiltrating NK cells from NOD4.1 mice expressing the degranulation marker CD107a. Diabetogenic CD4(+) T cells transferred disease to NODscid.IL2Rγ(-/-) mice lacking NK cells, indicating that NK cells do not contribute to β-cell death in vitro or in vivo. However, depletion of NK cells reduced diabetes incidence in NOD4.1 mice, suggesting that NK cells may help to maintain the right environment for cytotoxicity of effector cells.
authors.affiliation: St Vincent's Institute, Fitzroy, Melbourne, Australia.
authors.forename: Eveline
authors.initials: E
authors.lastname: Angstetra
authors.forename: Kate L
authors.initials: KL
authors.lastname: Graham
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Allison E
authors.initials: AE
authors.lastname: Irvin
authors.forename: Lorraine
authors.initials: L
authors.lastname: Elkerbout
authors.forename: Pere
authors.initials: P
authors.lastname: Santamaria
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Slattery
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kay
authors.forename: Helen E
authors.initials: HE
authors.lastname: Thomas
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics
chemical_list: D015234:HLA-A Antigens; D052118:Lysosomal-Associated Membrane Protein 1; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse; D015375:Receptors, Interleukin-2